Dietary polyunsaturated fatty acids (PUFAs) have effects on diverse physiological processes impacting normal health and chronic diseases, such as the regulation of plasma lipid levels, cardiovascular and immune functions, insulin action, neuronal development and visual function.
Due to their limited stability in vivo and their lack of biological specificity, PUFAs have not achieved widespread use as therapeutic agents. Chemical modifications of the n-3 polyunsaturated fatty acids have been performed by several research groups in order to change or increase their effects.
For example, the hypolipidemic effects of (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (DHA) was potentiated by introducing a substituent in the α-position of (4Z,7Z,10Z,13Z,16Z,19Z)-ethyl docosa-4,7,10,13,16,19-hexaenoate (DHA EE). (WO 2006/117664) It is reported that obese, high fat-fed mice treated with alpha-substituted DHA derivatives prevented and reversed obesity and glucose intolerance. (Rossmeisl, M., et al., Obesity (Silver Spring) 2009 Jan. 15.)
Several research groups have prepared unsaturated fatty acids with oxygen incorporated in the β-position (Flock, S. et al., Acta Chemica Scandinavica, (1999) 53: 436 and Pitt, M J, et al., Synthesis, (1997) 1240-42).
A novel group of fatty acid derivatives combining an oxygen atom in β-position with a α-substituents represented by the general formula (I) has been developed. These novel fatty acids reduce lipid levels in a dyslipidemic mice model to a greater extent than naturally occurring polyunsaturated fatty acids.